Human, cancers frequently express high levels of transmembrane tyrosine kinases of the Her family. Overexpression of at least one of these, the Her2 receptor, has been associated with a more aggressive behavior. Several therapeutic strategies targeting the receptor are now in various stages of clinical development. Most of the known agents block the activation or inhibit the activity of Her2; however, a more significant therapeutic outcome may result from degrading this oncoprotein. We propose here a cell-based assay that may be used to conduct high-throughput screens (HTS) to isolate Her2 kinase expression inhibitors. The compounds identified from these efforts will represent important leads that will serve as the starting point to obtain drugs that modulate Her2 expression. These drugs could, in principle, be used to treat patients with advanced cancers driven by Her2-overexpression/oversignalling. Given the importance of Her-kinases in human disease, the time is ripe to design and perform a large-scale screening regimen to identify Her-kinase expression modulators. To our knowledge, this has not been accomplished, and we believe that we are uniquely positioned to initiate this goal. [unreadable] [unreadable]